17-29593661-G-C

Position:

• chr17-29593661-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152345.5(ANKRD13B):​c.40G>C​(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000469 in 1,278,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: ANKRD13B NM_152345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

Genes affected

ANKRD13B (HGNC:26363): (ankyrin repeat domain 13B) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of receptor internalization. Located in endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13B (HGNC:):

GIT1 (HGNC:4272): (GIT ArfGAP 1) Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2394962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5	c.40G>C	p.Gly14Arg	missense_variant	1/15	ENST00000394859.8	NP_689558.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000394859.8	c.40G>C	p.Gly14Arg	missense_variant	1/15	2	NM_152345.5	ENSP00000378328.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000469 AC: 6 AN: 1278334 Hom.: 0 Cov.: 30 AF XY: 0.00000317 AC XY: 2 AN XY: 630130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000592

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.40G>C (p.G14R) alteration is located in exon 1 (coding exon 1) of the ANKRD13B gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	0.0022	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.61	T;.
M_CAP	Pathogenic	1.0	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	0.21	.;N
REVEL	Uncertain	0.34
Sift	Benign	0.46	.;T
Sift4G	Benign	0.40	T;T
Polyphen		0.016	B;B
Vest4		0.26
MutPred		0.49		Gain of MoRF binding (P = 0.0217);Gain of MoRF binding (P = 0.0217);
MVP		0.86
MPC		1.3
ClinPred		0.14	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27920679;